In an apparently paradoxical response, experimental diabetes mellitus stimulates the function of the intestinal brush border membrane with increases in the activities of many active transport systems and membrane-bound hydrolases. In an effort to determine the mechanism of this response, we studied sucrase as a representative brush border membrane hydrolase stimulated by diabetes. Our findings indicated that diabetic enhancement of sucrase activity occurs because of a decrease in rate of degradation of sucrase-isomaltase protein. Although sucrase-isomaltase is degraded extracellularly, other hydrolases stimulated in diabetes are degraded intracellularly, suggesting that the primary alteration is in the susceptibility of these membrane proteins to degradation, rather than in the degradative prcess itself. To test this hyopothesis, we propose to study rates of degradation (and synthesis) of trehalase, a brush border hydrolase which is also stimulated in diabetes, but is degraded intracellularly. If degradation of trehalase is also decreased in diabetes, the case for a primary effect on susceptibility to degradation will be much stronger. Changes in susceptibility of these proteins to degradation suggest alterations in the lipid bilayer. This is especially attractive because of the evidence that diabetes affects both lipid composition and enzyme activities of plasma membranes in other tissues. Therefore, we propose to study the effects of experimental diabetes on the composition of brush border membrane lipids, to look for evidences of an altered physical state of membrane lipids in diabetes by studying the behavior of membrane-bound enzymes, and to investigate the metabolism of membrane proteins when brush border lipids are altered by other means (diet).